Drug release characteristics of gatifloxacin-poly sebacic anhydride local controlled release system / 中国组织工程研究

ABSTRACT

BACKGROUND:High-dose antibiotics for bone infection have many adverse reactions, and its outcomes are not perfect. Thus, to explore a degradable material as a vector to prevent bone infection is valuable. OBJECTIVE:To study drug release characteristics of gatifloxa-poly sebacic anhydride local control ed release system in vivo. METHODS:A 3 mm × 6 mm bone window was made at right knee joint of New Zealand rabbits. The gatifloxacin-poly sebacic anhydride sustained release preparation was implanted. Heart blood, bone tissue and myeloid tissue specimens were obtained at 1, 2, 3, 6, 9, 12, 15, 18, 25 and 30 days after surgery. High-performance liquid chromatography was utilized to determine gatifloxacin concentration. Scanning electron microscope was employed to observe the structural changes before and after implantation of gatifloxacin-poly sebacic anhydride sustained release preparation. RESULTS AND CONCLUSION:After implantation of gatifloxacin-poly sebacic anhydride sustained release preparation, drug concentration gradual y decreased in the myeloid tissue, peaked at 1 day, stabilized at 3-15 days, gradual y reduced at 15-30 days. However, the drug concentration was stil higher than the minimal inhibitory concentration 0.1 mg/L against Staphylococcus aureus at 30 days. The peak of drug concentration in the bone tissue occurred at 3 days, and stabilized at other days, which was higher than 0.1 mg/L. At the same time point, drug concentration in the blood specimen was lower than that in the myeloid tissue and bone tissue. The degradation of gatifloxacin-poly sebacic anhydride sustained release preparation was surface erosion, and the shape of the degradation residue is smal globular. The change of the internal structure of gatifloxacin-poly sebacic anhydride sustained release preparation was not found. In the drug release procedure, gatifloxacin-poly sebacic anhydride sustained release preparation did not show disintegration or fragmentation. These results indicated that gatifloxacin-poly sebacic anhydride local sustained release preparation has good abilities of drug load and drug release.